Acta Neuropsychiatrica最新文献

Background: Late-life depression (LLD) arises from a complex interplay among biological, psychological, and social factors. Biologically, three main hypotheses have been proposed to explain the distinct clinical features of LLD. The vascular hypothesis supports vascular-related white matter changes in the development of LLD, while the neurodegenerative hypothesis suggests that LLD might be a prodrome of neurodegenerative diseases. The inflammatory hypothesis, which is the main focus of this review, posits that heightened inflammation underlies LLD directly or indirectly through neurodegenerative and microvascular alterations.

Methods: This is a non-systematic review on the role played by inflammation in the pathophysiology of LLD and the related opportunities to define biomarkers and therapeutic targets. We searched PubMed from January 2010 through March 2025 for relevant English-language studies.

Results: Patients with LLD have elevated circulating levels of inflammatory biomarkers (e.g., C-reactive protein and interleukin-6) as well as evidence of neuroinflammation. Although the exact origin of this inflammatory profile remains unclear, it is thought to be exacerbated by immune cell senescence and the presence of physical comorbidities, including cardiovascular and metabolic diseases. Pharmacological (e.g., selective serotonin receptor inhibitors) and non-pharmacological (e.g., diet, physical interventions) approaches for LLD seem to exert their therapeutic effect, at least in part, through inflammation-related mechanisms.

Conclusion: Recognizing the unique features of LLD compared to depression in other periods of life is an important step toward its proper management. More specifically, understanding the role of inflammation in LLD holds both theoretical and practical implications, including anti-inflammatory or immune-based strategies as potential therapeutic interventions.

Objectives: The present study examines the quality of life (QoL) of transgender and gender-diverse individuals receiving versus not receiving gender-affirming hormone therapy (GAHT) in those assigned male at birth (AMAB) and assigned female at birth (AFAB). It also explores the relationship between QoL and concentrations of oestradiol and testosterone.

Methods: This cross-sectional study used the WHOQOL-BREF questionnaire to assess QoL. Participants were categorised into four groups based on assigned sex at birth (AMAB or AFAB) and GAHT status, with non-GAHT participants serving as controls. MANOVA and t-tests were used to compare QoL between groups, and linear regression analyses examined associations between QoL and oestradiol/testosterone concentrations in AMAB and AFAB participants.

Results: The study included 360 participants: 169 AMAB (143 GAHT, 26 controls) and 191 AFAB (141 GAHT, 50 controls). GAHT recipients had significantly higher QoL than controls in both AMAB (p < 0.01) and AFAB (p = 0.02) groups, particularly in the psychological health domain (D2). AFAB participants reported higher overall QoL than AMAB in both GAHT (p = 0.01) and control (p = 0.04) groups, with significance in the social domain among GAHT participants. No significant relationship was found between oestradiol concentrations and QoL for participants AMAB. However, a significant relationship between testosterone concentrations and QoL was observed only in the social relationship domain (D3) for participant AFAB.

Conclusion: This study highlights the benefits of GAHT for QoL and differences in QoL between AMAB and AFAB individuals.

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterised by impairments in social communication, repetitive behaviours, and restricted interests. Emerging evidence suggests that immune system dysregulation, particularly alterations in the complement system, may contribute to ASD pathophysiology. This study aimed to compare the serum levels of complement proteins (C1q, C2, C3, C4, MBL, L-ficolin, and hsCRP) between children with ASD and non-ASD controls. A total of 88 children (44 with ASD and 44 age- and sex-matched healthy controls) participated in this study. Complement protein levels were measured using enzyme-linked immunosorbent assay (from serum samples. The severity of ASD symptoms was assessed using standardised diagnostic tools, including the Childhood Autism Rating Scale, the Autism Behaviour Checklist, and the Repetitive Behaviour Scale-Revised. Serum C1q levels were significantly lower in the ASD group (p < 0.001). C3 levels were lower (p = 0.033), while C2 levels were slightly higher (p = 0.015) in the ASD group. There are no significant differences in C4, MBL, or L-ficolin levels. Logistic regression analysis identified reduced C1q levels as a significant predictor of ASD (p = 0.001). However, this study found no significant correlations between complement levels and ASD symptom severity scores. The findings suggest that alterations in complement system proteins, particularly reduced serum C1q levels, may be associated with ASD. Given C1q’s critical role in synaptic pruning and neuroimmune regulation, these results support the hypothesis that complement system dysfunction may contribute to the pathophysiology of ASD.

Objective: This systematic review aims to update the current evidence on the effects of institutionalisation in minors living in residential care homes, specifically focusing on alterations in neuronal systems and their association with psychopathological and neuropsychological outcomes.

Methods: Searches were conducted in the Web of Science, Scopus, PubMed, and Google Scholar databases, following PRISMA methodology for peer-reviewed empirical articles. The final selection comprised 10 studies that met the inclusion criteria: (1) published articles with quantitative data, (2) aimed at observing the relationship between psychological and neuropsychological symptoms and the electroencephalogram (EEG) activity in institutionalised children, (3) published between 2016 and 2023, and (4) examining institutionalised minors in residential care homes.

Results: The articles show that these children exhibit general immaturity in EEG patterns, with a predominance of slow waves (primarily in the theta band). They also demonstrate poorer performance in executive functions (e.g. working memory, inhibition, and processing speed) and cognitive processes, along with a higher risk of externalising problems. However, current evidence does not allow definitive conclusions on whether early EEG abnormalities predict long-term neuropsychological deficits, despite data showing associations between EEG changes and certain cognitive dysfunctions at the time of evaluation.

Conclusion: The reviewed evidence suggests that EEG alterations in institutionalised minors are linked to executive dysfunction and increased psychopathological risk. These findings highlight the value of EEG in identifying at-risk children and inform the design of preventive interventions. Longitudinal studies are needed to clarify causal relationships.

Acceptance and commitment therapy (ACT) is recognised as an effective treatment for a variety of mental illnesses. Several meta-analyses have reported the efficacy of ACT in various mental and physical conditions, including depression, anxiety, and pain, but not for suicidality. This study aimed to determine the therapeutic effectiveness of ACT on suicidality through a systematic review and meta-analysis. Electronic databases such as PubMed, Embase, Scopus, and the Cochrane Library were searched for studies. The primary outcome measure was the effectiveness of ACT for suicidality which includes suicidal ideations and attempts. This systematic review and meta-analysis included eight studies, all of which were judged to have a high risk of bias. In the meta-analysis, the pooled standardised mean difference for suicidal ideations was 1.122 (95% confidence interval (CI) = 0.261 to 1.982). This meta-analysis suggests that ACT is effective for reducing suicidal ideation, but the high risk of bias across studies should be considered as a major limitation. Further well-designed studies are needed to confirm these findings.

Objective: Kabuki syndrome is a rare multisystem congenital disorder characterised by specific facial malformations and several other symptoms, including motor impairments, increased susceptibility to infections, immune mediators' deficits, anxiety, and stereotyped behaviours. Considering the reports of motor impairments in Kabuki syndrome patients, the first hypothesis of the present study was that this motor dysfunction was a consequence of striatal dopaminergic modulation. The second hypothesis was that the peripheral immune system dysfunctions were a consequence of neuroinflammatory processes. To study these hypotheses, the mutant bapa mouse was used as it is a validated experimental model of Kabuki syndrome.

Methods: Exploratory behaviour, anxiety-like behaviour (light-dark test), repetitive/stereotyped behaviour (spontaneous and induced self-grooming), and tyrosine hydroxylase (TH), astrocyte glial fibrillary acidic protein (GFAP), and ionised calcium-binding adaptor molecule 1 (Iba1) striatal expressions were evaluated in female adult bapa and control mice.

Results: Female bapa mice did not present anxiety-like behaviour, but exploratory hyperactivity and stereotyped behaviour both on the spontaneous and induced self-grooming tests. Striatal TH, GFAP, and Iba1 expressions were also increased in bapa mice.

Conclusion: The exploratory hyperactivity and the stereotyped behaviour occurred in detriment of the striatal dopaminergic system hyperactivity and a permanent neuroinflammatory process.

Objective: Compulsive-like rigidity may be associated with hyposerotonergia and increased kynurenine (KYN) pathway activity. Conversion of tryptophan (TRP) to KYN, which may contribute to hyposerotonergia, is bolstered by inflammation and could be related to altered gut microbiota composition. Here, we studied these mechanisms in a naturalistic animal model of compulsive-like behavioural rigidity, that is, large nest building (LNB) in deer mice (Peromyscus sp.).

Methods: Twenty-four (24) normal nest building (NNB) and 24 LNB mice (both sexes) were chronically administered either escitalopram (a selective serotonin reuptake inhibitor; 50 mg/kg/day) or a control solution, with nesting behaviour analysed before and after intervention. After endpoint euthanising, frontal cortices and striata were analysed for TRP and its metabolites, plasma for microbiota-derived lipopolysaccharide (LPS) and its binding protein (lipopolysaccharide binding protein), and stool samples for microbial DNA.

Results: LNB, but not NNB, decreased after escitalopram exposure. At baseline, LNB was associated with reduced frontal cortical TRP concentrations and hyposerotonergia that was unrelated to altered KYN pathway activity. In LNB mice, escitalopram significantly increased frontal-cortical and striatal TRP without altering serotonin concentrations. Treated LNB, compared to untreated LNB and treated NNB mice, had significantly reduced plasma LPS as well as a microbiome showing a decreased inferred potential to synthesise short-chain fatty acids and degrade TRP.

Conclusions: These findings support the role of altered serotonergic mechanisms, inflammatory processes, and gut microbiome involvement in compulsive-like behavioural rigidity. Our results also highlight the importance of gut-brain crosstalk mechanisms at the level of TRP metabolism in the spontaneous development of such behaviour.

Suicidality is a significant public health concern, with neuroimaging studies revealing abnormalities in the brains of suicidal individuals and post-mortem samples. However, the genetic architecture between suicidality and subcortical brain volumes remains poorly characterized. Using genome-wide association studies (GWAS), we investigated the genetic overlap between suicidality and subcortical brain volume. GWAS summary statistics for suicidal behaviours, including Suicide Attempts, Ever Self-Harmed, and Thoughts of Life Not Worth Living, from the UK Biobank, Suicide from the FinnGen Biobank, and data on seven subcortical brain volumes and Intracranial Volume from the ENIGMA2 study, were used to investigate the genetic correlation between phenotypes as well as potential genetic factors. A common genetic factor was identified, comprising two categories: Suicide Attempt, Ever Self-Harmed, and Thoughts of Life Not Worth Living from the UK Biobank, and Suicide from FinnGen, Intracranial Volume, and subcortical brain volumes. Cross-phenotype GWAS meta-analysis of each category at variant, gene and subnetwork levels unveils a list of significant variants (P-value <5 × 10^-8), and potential hub genes (P-value <0.05) of consideration. Network, pathway, and Gene Ontology analyses of these joint categories highlighted enriched pathways and biological processes related to blood-brain barrier permeability suggesting that the presence and severity of suicidality are associated with an inflammatory signature detectable in both blood and brain tissues. This study underscores the role of brain and peripheral blood inflammation in suicide risk and holds promise for developing targeted interventions and personalized treatment strategies to reduce suicidality in at-risk populations.

This study focused on the effect of the cognitive behavioural therapy (CBT) combined with aripiprazole on cognitive functions and psychological state of schizophrenia patients. Seventy-eight schizophrenia patients were divided into two groups. One group received aripiprazole with conventional nursing treatment for 3 months (control group, n = 39), and the other received aripiprazole with CBT for 3 months (observation group, n = 39) (1 session per week, each session lasting 60 min. In the two groups before and after treatment, the severity of symptoms was evaluated using the Psychiatric Symptom Rating Scale (BPRS). Cognitive function was assessed with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The Positive and Negative Symptom Scale (PANSS) was utilised to evaluate mental status, while the Generalised Self-Efficacy Scale (GSES) measured psychological state. Additionally, the quality of life was assessed using the General Quality of Life Inventory-74 (GQOLI-74). In the final analysis, post-treatment efficacy and complications for the two groups were counted. Both groups showed significant improvements: BPRS and PANSS scores decreased, while RBANS, GSES, and GQOLI-74 scores increased. The observation group showed greater improvements than the control group. The total improvement rate was 89.74% (35/39) in the observation group, higher than the 71.79% (28/39) in the control group. The complication rate was 33.33% (13/39) in the observation group and 38.46% (15/39) in the control group. The treatment of CBT combined with aripiprazole for schizophrenia has a significantly positive effect on the cognitive functions and psychological state of patients.

Objectives: Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) are collectively called as Lewy body dementia (LBD). Despite the urgent clinical need, there is no reliable protein biomarker for LBD. Hence, we conducted the first comprehensive systematic review of all Differentially Abundant Proteins (DAP) in all tissues from people with LBD for advancing our understanding of LBD molecular pathology that is essential for facilitating discovery of novel diagnostic biomarkers and therapeutic targets for LBD.

Methods: We identified eligible studies by comprehensively searching five databases and grey literature (PROSPERO protocol:CRD42020218889). We completed quality assessment and extracted relevant data. We completed narrative synthesis and appropriate meta-analyses. We analysed functional implications of all reported DAP using DAVID tools.

Results: We screened 11,006 articles and identified 193 eligible studies. 305 DAP were reported and 16 were replicated in DLB. 37 DAP were reported and three were replicated in PDD. Our meta-analyses confirmed six DAP (TAU, SYUA, NFL, CHI3L1, GFAP, CLAT) in DLB, and three DAP (TAU, SYUA, NFL) in PDD. There was no replicated blood-based DAP in DLB or PDD. The reported DAP may contribute to LBD pathology by impacting misfolded protein clearance, dopamine neurotransmission, apoptosis, neuroinflammation, synaptic plasticity and extracellular vesicles.

Conclusion: Our meta-analyses confirmed significantly lower CSF TAU levels in DLB and CSF SYUA levels in PDD, when compared to Alzheimer's disease. Our findings indicate promising diagnostic biomarkers for LBD and may help prioritising molecular pathways for therapeutic target discovery. We highlight ten future research priorities based on our findings.